Novel substituted calix (4) pyrroles and process for the synthesis of calix (4) pyrroles over molecular sieve catalysts

ABSTRACT

The present invention relates to novel calix pyrroles and a process for synthesis of calix (4) pyrroles by reacting pyrrole with cyclic or acyclic ketones in dichloro methane (DCM) solvent over molecular sieve catalysts which provides an eco-friendly, more economical and selective heterogeneous method.

FIELD OF THE INVENTION

[0001] The present invention relates to novel calix (4) pyrroles andpreparation of calix (4) pyrroles over zeolite molecular sieves. Moreparticularly, this invention relates to a method for synthesis of calix(4) pyrroles directly from pyrroles and ketones in an eco-friendlyzeolite catalyzed heterogeneous method with high yields.

[0002] This invention provides a non-corrosive eco-friendly process,where the catalyst is recyclable and reused many times, no work upprocedure, no-wastage of the compounds (i.e. high atom selectivity),simple sample extraction and high selectivity of products.

BACKGROUND AND PRIOR ART REFERENCES

[0003] Calix pyrroles represent a subset of class of macrocycles thatwas previously termed as porphyrinogens. Porphyrinogens arenon-conjugated macrocyclic species composed of four pyrrole rings linkedto the position via sp³ hybridized carbon atoms. Porphyrinogens thatcarry meso-hydrogen atoms are prone to oxidation to the correspondingphorphyrins and renamed the term porphyrinogen as calixpyrrole due tothe analogues properties of calixarenes. Fully meso non-hydrogensubstituted phorphyrongens are generally stable crystalline materials.The first such macrocycle, meso octamethyl calix (4) pyrrole wasreported over a century ago by Bayer (Ber. Disctz. Chem. Ger. 1886, 19,2184) using condensation between acetone and pyrrole catalyzed by HCl,however, the structure of the molecule was not elucidated. This methodwas refined by Dennstedt and Zimmerman (Ber. Disctz. Chem. Ger. 1887,20, 850) by replacing the HCl with “chlorzink” and heating the reaction.Chelintzev and Toronov synthesized calix (4) pyrrole by the method ofcondensing acetone and pyrrole, methyl ethyl ketone and pyrrole, methylhexyl ketone and pyrrole and a mixture of acetone and methyl ethylketone with pyrrole (J. Russ. Phys. Chem. Soc. 1916, 48, 1197; ChemAbstr. 1917, 11, 1418). Further, Chelintzev, Tronov and Kurmunovreported the production of calixpyrroles by condensing cyclohexanonewith pyrrole and a mixture of acetone and cyclohexanone with pyrrole (J.Russ. Phys. Chem. Soc. 1916, 48, 1210). Rothenmund and Gage refinedDennstedt and Zimmermann's method by replacing the acid catalyst withmethane sulphonic acid (J. Am. Chem. Soc. 1955, 55, 3740). In 1971,Brown, Iluichioson and Mackinon (Can. J. of Chem. 1971, 49, 4017)repeated the synthesis of mesotetracyclohexyl calixpyrrole and assigneda tetrameric macrocyclic structure. J. M. Lehn and coworkers havesynthesized meso-octa-3-chloro propyl calix (4) pyrrole by anunpublished procedure and converted into meso-octa-3-cyano propyl calixpyrrole (B. Dietrich, P. Viout and J. M. Lehn in macrocyclic chemistry,VCH, Publishers, Weinhein 1993, pg82). The metal cation binding ofdeprotanated calix (4) pyrrole macrocyclics has been studied by Florianiand co-workers (Chem. Commun. 1996, 1257). Floriani has developed amethod for expanding the pyrrole rings of metal bound deprotanated calix(4) pyrroles forming calix (1) pyridino (3) pyrroles and calix (2)pyridino (2) pyrroles (J. Am. Chem. Soc. 1995, 117, 2793). A further aprior art method reports using pyrrole, a C₄-C₆ saturated acyclic ketoneand an acid containing vinyl groups are triple bonds to form apolymerized resin (WO 93/13150). In this case, the resulting productsare undefined, since it appears to be unknown where the modifying groupis attached to the product. By making use of calixarenes as templates P.A. Gale et al synthesized Calixarene-calix pyrrole dimers (calixarenecapped-calixpyrrole) and expanded calixpyrroles (Tet Lett 37(44),1996,7881) and also reported the synthesis of calixpyridino pyrroles andcalix pyridines from calixpyrroles (Chem corn 1998, 1). Macrocycles haveunexpected properties that make them particularly useful. Calixpyrrolesbind anion and neutral molecular species in solution and in the solidstate in such an effective and selective way the anions or neutralmolecular species can be separated from other anions and neutralmolecular species. Further the affinity a macrocycle has for aparticular species can be ‘tuned’ by strategic choice ofelectron-donating or electron-withdrawing peripheral substituents forthe synthesis of macrocycles.

[0004] According to W.O.Pat.No. 97/37995, various types of calixpyrroleswas synthesized using different ketones includingtetrahydrothiopyran-4-one, diphenylacetone, 10-nonadecanone, acetylferrocenes and chiral calixpyrroles by using chiral ketones. And alsoreported the synthesis of expanded calixpyrroles, where n>4, (i.e. Calix(5) pyrrole, Calix (6) pyrrole, calix (8) pyrroles), calix pyridinopyrroles, calix pyridines and their applications. Application of theseproperties for removal of biological ions or neutral molecule speciesfor medical uses, removal of undesirable ions or neutral moleculespecies from environmental sources provides only a few of the practicaland important uses.

[0005] These calix (4) pyrroles can be used in the dialysis of bodilyfluids. Examples of dialyzable substrates include, but are not limitedto phosphate containing molecules or halide waste (i.e. diabetes or drugoverdoses and kidney dialysis).

[0006] Clean technology is fast replacing the various processes, whichwere once catalyzed by highly corrosive liquid acids, due to the growingconcern for the environment. In these eco-friendly processes, solidacids which are highly selective and active with strong proton donatingsites distributed uniformly within the pores, have been found to be anattracting replacement for the non-reusable, hazardous liquid acids.Porous materials created by nature or by synthetic have found greatutility in all aspects of human activity. The pore structure of solidsis usually formed in the stages of crystallization or subsequenttreatment. Depending on their predominant pore size, the solid materialsare classified as microporous, mesoporous and macroporous materials. Theonly class of porous materials possessing rigorously uniform pore sizesis that of Zeolites and related molecular sieves. Zeolites are uniformporous crystalline aluminosilicates and their lattice is composed by TO₄tetrahedral (T=Al and Si) linked by sharing the apical oxygen atoms(Breck D. W., Zeolite molecular sieves: Structure, Chemistry and Use;Wiley and Sons; London 1974). As Zeolites act as sieves at the molecularlevel, these are considered as a subclass of molecular sieves. Zeoliteshave a number of interesting physical and chemical properties. Theclasses of phenomena that are of greatest practical importance are theavailability to sorb organic and inorganic substances, to act as cationexchangers and to catalyze a wide variety of reactions. But due to thesmaller pore size of these molecular sieves restricted their wide rangeapplications, especially in case of larger molecules. But this has beenovercome by the report of Mesoporous molecular sieves by Mobilresearchers (C. T. Kresge, M. E. Leonowicz, W. J. Roth, J. C. Vartuliand J. S. Beck, Nature 359 (1992) 710) in 1992. These Mesoporousmolecular sieve (MCM-41) has been opened a new era in the zeolitecatalysis. Till then many reports have been published on theapplications of this material for the catalytic activity towardsoxidation, acylation and alkylation. And support material for enzymes,whole cell immobilization, and nano particles.

[0007] The previous processes have the disadvantage that (a) in all thecases mineral acids used as catalysts which are highly corrosive, (b) inall the cases inert atmosphere should be maintained, (c) in all thecases tedious work-up procedure is present, such as neutralization ofacid etc, (c) separation and reusability of the catalyst is notpossible, (d) in some cases more than a single step is carried out toget a particular calix pyrrole selectively, and (e) in some cases dryconditions should be maintained in order to obtain the correspondingcompound.

[0008] Increasing the applications of these calix pyrroles demands aneco-friendly, environmentally clean, economical and free handlingprocess. The present invention provides an eco-friendly process, whichcan overcome all the above drawbacks.

OBJECTS OF THE INVENTION

[0009] The main object of the present invention is to provide calix (4)pyrroles over zeolite molecular sieves, which is an eco-friendlyheterogeneous catalytic method.

[0010] Another object of the present invention is to provide a processfor the synthesis of novel calix (4) pyrroles such astetraspirocycloheptyl calix (4) pyrrole, tetraspirocyclooctyl calix (4)pyrrole and tetraspiro (2-methylcyclohexyl) calix (4) pyrrole withsufficiently good yields.

[0011] Still another object of the present invention is to synthesizecalix (4) pyrroles over molecular sieve catalysts under microwaveirradiation, which is a solvent free reaction.

[0012] Yet another object is to provide a method wherein the kind andcomposition of calix (4) pyrrole can be varied within limits by a properselection of catalyst.

[0013] Yet another object of this invention is to provide an efficientand economical method for synthesizing calix (4) pyrroles from pyrroleand ketones over solid acid catalysts.

SUMMARY OF THE INVENTION

[0014] The present invention relates to novel calix (4) pyrroles and aprocess for synthesis of calix (4) pyrroles as shown in FIGS. 1 to 8 ofthe accompanying drawings, from corresponding pyrrole and ketone overmesoporous molecular sieves. Macrocycles of the present invention can beselectively synthesized by taking the different pore sizes of thezeolites and by varying the reaction conditions.

DETAILED DESCRIPTION OF INVENTION

[0015] The present invention relates to novel calix (4) pyrroles and aprocess for synthesis of calix (4) pyrroles over mesoporous molecularsieves. The invention particularly relates to heterogeneous eco-friendlymethodology for the synthesis of calix (4) pyrroles by using pyrrole andketone in dichloromethane solvent. Specifically, the present inventionrelates to the synthesis calix (4) pyrroles from corresponding pyrroleand ketone over mesoporous (Mesoporous molecular sieve) MCM-41 molecularsieves with a high yield and selectivity. In an embodiment of theinvention, the catalyst is selected from MCM-41, HZSM-5 (30), Hβ, HY andSAPO-5.

[0016] In another embodiment of the invention, the catalysts MCM-41,HZSM-5(30), Hβ, HY and SAPO-5 are conventional zeolite catalysts.

[0017] In another embodiment of the invention, the amount of catalystused is ranging from 0.1 g to 1.0 g.

[0018] In still another embodiment of the invention, the solvent usedfor refluxing is selected from dichloromethane, methanol, andacetonitrile.

[0019] In yet another embodiment of the invention, the catalysts usedare having the following surface area and pore size as given in thetable below. Catalyst Surface area (m²/g) Pore size (Å) MCM-41  980-120030-100 HY 525-625 6-8 HZSM-5 (30) 275-340 5-7.5 SAPO-5 175-240 6.5-8.4Hβ 600-680 5.5 × 6.6 to 7.5 × 8.5

[0020] In yet another embodiment of the invention, the pore size andsurface area of the catalysts used in the reaction are given in thefollowing table. Catalyst Surface area (m²/g) Pore size (Å) HY 593 7.3HZSM-5 (30) 310 5.6 SAPO-5 207 7.4 Hβ 640 6.5 × 7.6

[0021] In yet another embodiment of the invention, the molar ratio ofpyrrole to ketone is selected in between 1:1 to 1:4.

[0022] In yet another embodiment of the invention, the cycloketone isselected from the group comprising cyclohexanone, cycloheptanone,cyclopentanone and cyclooctanone.

[0023] In yet another embodiment of the invention, the acyclic ketone isselected from the group comprising methyl ethyl ketone and 3-pentanone.

[0024] In yet another embodiment of the invention, acyclic products areobtained using the catalyst HY.

[0025] In yet another embodiment of the invention, major amounts ofliner products are obtained using catalyst HZSM-5 (30).

[0026] In yet another embodiment of the invention, the yield of thecalix (4) pyrrole is up to 70%.

[0027] In yet another embodiment of the invention, the selectivity ofthe calix (4) pyrrole is up to 90%.

[0028] In one more embodiment of preparing calix (4) pyrroles ortetraspiro calix (4) pyrroles, said method comprising mixing a pyrrolewith a acyclic or cyclic ketones over a molecular sieve solid acidcatalyst and subjecting the mixture to microwave radiation at aradiation level of about 2450 MHz (Hl power) for 3 to 10 minutes andoptionally, refluxing using a solvent for extracting the compounds.

[0029] In another embodiment, the solvent used for refluxing is selectedfrom dichloromethane, methanol, and acetonitrile.

[0030] In yet another embodiment of the present invention, in theequimolar reaction, the molar ratio of pyrrole to ketone is 1:1 anddichloromethane is used as a solvent for refluxing to obtain cyclicproducts.

[0031] In yet another embodiment, the catalyst used is mesoporusmolecular sieve catalyst (MCM-41).

[0032] In yet another embodiment, the acyclic ketone used is acetone.

[0033] In yet another embodiment, the cyclic ketone used iscyclohexanone.

[0034] In yet another embodiment, the preparation of calix (4) pyrrolesor tetraspiro calix (4) pyrroles is a solvent free process.

[0035] The catalyst can be synthesized from the well known definedmethods. The starting materials used in the process are acyclic andcyclic ketones, which are readily available. Reacting the pyrrole withacyclic ketones, which are selected from acetone, methyl ethyl ketone,and 3-pentanone leads to form octamethyl calix (4) pyrrole, tetramethyltetraethyl calix (4) pyrrole, and octaethylcalix (4) pyrrolescorrespondingly.

[0036] In case of cyclic ketones, cyclohexanone, cyclopentanone,cycloheptanone, 2-methylcyclochexanone, cyclo octanone formstetraspirocyclochexyl calix (4) pyrrole, tetraspirocyclopentyl calix (4)pyrrole, tetraspirocycloheptyl calix (4) pyrrole, tetraspiro(2-methylcyclohexyl) calix (4) pyrrole and tetraspirocyclooctyl calix(4) pyrrole correspondingly.

[0037] The catalyst MCM-41 (Mesoporous molecular sieve) prepared by anaqueous solution of aluminum isopropoxide (0.38 g) and to it an aqueoussolution of sodium hydroxide (0.3 g) was added in 50 ml beaker andstirred in hot conditions, till a clear solution was formed. Then 9.4 mlof tetraethyl ammonium hydroxide (TEAOH) and Ludox colloidal silica(9.26 g) were added drop wise while stirring at room temperature. Thenhexadecyl tri-methylammonium bromide (10.55 g) was added slowly to theabove solution. The pH of the mixture was maintained at 11.0-11.5.Finally, the gel mixture was transferred into an autoclave and heated at100° C. for 24 h. The solid product was recovered by filtration, washedwith deionized water and dried in air. All the as-synthesized sampleswere calcined at 773K in air.

[0038] The catalyst weight can be varied in this reaction from 0.1 g to1 g. The pyrrole to acetone molar ratio can be varied from 1:1 to 1:4.

[0039] In the reaction, an equimolar ratio of pyrrole and cyclohexanonewas refluxed in dichloromethane (DCM) for 10 h in presence of MCM-41catalyst. Along with the cyclized product, tetraspirocyclo hexyl calix(4) pyrrole 4a, the acyclic condensed products viz., dimer, trimer andtetramer (4b, 4c and 4d) were also formed.

[0040] In place of MCM-41catalyst when HY was used, instead of cyclicproduct only the acyclic products were formed.

[0041] When HZSM-5 (30) was used as catalyst, along with the cyclizedproduct calix (4) pyrrole, linear products also formed but the linearproducts are in major.

[0042] When Hβ was used as catalyst, along with the cyclized productcalix (4) pyrrole, linear products are also formed.

[0043] The reaction time will be varied depending upon the nature ofketone and the catalyst. In the one of equimolar reaction, pyrrole andacetone was mixed thoroughly and 0.5 gm of MCM-41 catalyst was added andthen subjected to microwave irradiation for 3 min at a radiation levelof about 2450 MHz and extract the compound by using dichloromethane assolvent, resulting low selectivity of cyclic product (1a). The reactiontime is varied from 3 min to 10 min.

[0044] In another equimolar reaction, pyrrole and cyclohexanone wasmixed thoroughly and added 0.5 gm of MCM-41 catalyst and then subjectedto microwave irradiation for 3 min and extracted the compound by usingdichloromethane as solvent, resulting low selectivity of cyclic product(4a). The reaction time is varied from 3 min to 10 min. The radiationlevel is maintained at about 2450 MHz.

[0045] Mixed calix pyrroles such as tetramethyl dicyclohexyl calix (4)pyrrole, hexamethyl cyclohexyl calix (4) pyrrole, dimethyl tricyclohexyl calix (4) pyrrole has been obtained by reacting the acetone,cyclohexanone in required molar ratio over MCM-41 catalyst indicholoromethane solvent by refluxing for 15 h.

[0046] Pore size and surface area of the catalysts plays a major role inthis reaction.

[0047] All the catalysts were characterized by X-ray diffraction,Infrared spectroscopy, BET-surface area and NH₃-Temperature programmeddesorption.

[0048] The inventors found that the dichloromethane (DCM) was bettersolvent than other solvents like methanol, acetonitrile. Acetone assolvent did not found the selectivity towards higher selectivity ofoctamethyl calix (4) pyrrole.

[0049] After the reaction was completed the catalyst was separated byfiltration, then the solvent was vacuum evaporated and the residue wasmounted on the silica column and the products were separated throughn-hexane: ethylacetate (95:5) media and confirmed by H¹ NMR, C¹³ NMR andMass spectroscopy and for 1a, single crystal XRD also.

BRIEF DESCRIPTION OF THE ACCOMPANYING DRAWINGS

[0050]FIG. 1 shows structure of octa alkyl substituted calix (4)pyrrole, wherein

[0051] R₁ and R₂=CH₃ for octamethyl calix (4) pyrrole (1a),

[0052] R₁=CH₃ and R₂=CH₂CH₃ for Tetraethyl Tetra methyl calix (4)pyrrole (2a), and

[0053] R₁=R₂=CH₂CH₃ for octaethyl calix (4) pyrrole (3a).

[0054]FIG. 2 shows structure of tetraspiro cyclohexyl calix (4) pyrrole(4a).

[0055]FIG. 3 shows structure of tetraspiro cycloalkyl substituted calix(4) pyrrole

[0056] wherein,

[0057] n=1 for tetraspiro cyclopentyl calix (4) pyrrole (5a),

[0058] n=2 for tetraspiro cycloheptyl calix (4) pyrrole (6a), and

[0059] n=4 for tetraspiro cyclooctyl calix (4) pyrrole (7a).

[0060]FIG. 4 shows structure of (2-methyl cyclohexyl) calix (4) pyrrole(8a).

[0061]FIG. 5 shows structures of condensed products viz. dimer (4b),trimer (4c) and tetrameter (4d).

[0062]FIG. 6 shows structure of alkyl substituted linear (dimer)products, wherein

[0063] R₁ and R₂=CH₃ for 1a, R₁=CH₃ and R₂=CH₂CH₃ for 2a, and

[0064] R₁=R₂=CH₂CH₃ for 3a.

[0065]FIG. 7 shows structure of cyclic products, wherein n=1 for 5b; n=3for 6b and n=4 for 7b.

[0066]FIG. 8 shows structure of dimer product of 2-methylcyclohexyl(8b).

[0067] The process of this invention is described in further detailherein below by way of the following examples, which are onlyillustrative and are not intended to limit the scope of this invention.

EXAMPLES Example 1

[0068] Synthesis of Octamethyl Calix (4) Pyrrole

[0069] In a 50 ml round bottom flask, 20 ml of dichloromethane (DCM) wasintroduced and 0.5 ml of pyrrole, 0.503 ml of acetone, and 0.5 g ofMCM-41 catalyst were added to it. Then the reaction mixture was refluxedfor 10 h. The cooled reaction mixture filtered, washed with DCM (5×10ml). Then the solvent DCM was removed under reduced pressure and productwas purified by column chromatography on silicagel (hexane eluent)affording the product as a white powder. The product was confirmed byNMR and Mass spectrometry. Yield of octamethyl calix (4) pyrrole was67.5%; Selectivity was 73.0; Conversion of pyrrole was 92.4%.Selectivity was calculated as follows

Selectivity=Yield/Conversion

[0070] 1a: ¹HNMR (200 MHz, CDCl₃): δ=1.49 (s, 24H, —CH₃), 5.85 (br, d,8H; (pyrrole-βH), 6.89-6.99 (br, S, 4H, pyrrole-NH); HR-MS(EI): forcalcd for C₂₈ H₃₆ N₄: calcd: 428.2939; found: 428.2938.

Example 2

[0071] In a 50 ml round bottom flask 20 ml of dichloromethane (DCM) wasintroduced and 0.5 ml of pyrrole, 0.503 ml of acetone, and 0.5 g ofHZSM-5 (30) catalyst were added to it. Then the mixture was refluxed for10 h. The cooled reaction mixture filtered, washed with DCM (5×10 ml).Then the solvent DCM was removed under reduced pressure and product waspurified by column chromatography on silicagel (hexane eluent) theproducts were confirmed by NMR and estimation was done by high pressurethin layer chromatography (HPTLC). The Results are as follows:Conversion of pyrrole is 81.4%. Product Yield (wt %) Selectivity (%)Octamethyl calix(4)pyrrole (1a) 40.0 49.2 Trimer + tetramer 29.8 36.6Dimer (1b) 11.56 14.2

Example 3

[0072] In a 50 ml round bottom flask 20 ml of dichloromethane (DCM) wasintroduced and 0.5 ml of pyrrole, 0.503 ml of acetone, and 0.5 g of HYcatalyst was added to it. Then the mixture was refluxed for 10 h. Thecooled reaction mixture filtered, washed with DCM (5×10 ml). Then thesolvent DCM was removed under reduced pressure and product was purifiedby column chromatography on silicagel (hexane eluent) the products wereconfirmed by NMR and estimation was done by high pressure thin layerchromatography (HPTLC). The results as follows: conversion of pyrrole is72.5%. Product Yield (wt %) Selectivity (%) Octamethyl Calix(4)pyrroleTrimer + tetramer 14.0 19.3 Dimer 58.5 80.7

[0073] 1b: ¹HNMR (200 MHz, CDCl₃): δ=1.62 (s, 6H, —CH₃), 6.01-6.11 (m,4H, pyrrole-βH), 6.48-6.56 (m, 2H, pyrrole-αH), 7.42-7.78 9br, s, 2H,NH), ¹³C NMR (50 MHz, CDCl₃): δ=29.30, 35.32, 103.74, 107.72, 117.03,138.21; HR-MS (EI) for C₁₁H₁₄N₂: calcd: 174.1156; found: 174.1148

Example 4

[0074] Synthesis of Tetramethyl Tetraethyl Calix (4) Pyrrole

[0075] In a 50 ml round bottom flask 20 ml of dichloromethane (DCM) wasintroduced and 0.5 ml of pyrrole, 0.65 ml of Methyl ethyl ketone, and0.5 g of Al-MCM-41 catalyst was added to it. Then the mixture wasrefluxed for 72 h. The cooled reaction mixture filtered, washed with DCM(5×10 ml). Then the solvent DCM was removed under reduced pressure andproduct was purified by column chromatography on silicagel (hexaneeluent) the products were confirmed by NMR and estimation was done byhigh pressure thin layer chromatography (HPTLC). The results as follows:conversion of pyrrole is 48.0%. Product Yield (wt %) Selectivity (%)Tetraethyl tetramethyl calix(4)pyrrole (2a) 34.8 72.5 Trimer + tetramer4.5 9.4 Dimer (2b) 8.7 18.1

[0076] 2a: ¹HNMR (200 MHz, CDCl₃): δ=0.63-0.8 (t, J(H,H)=2 Hz, 12H),1.34-1.48 (br, s, 12H, -CH ₃, 1.86-1.96 (q, 8H, CH ₂CH₃), 5.85 (br, d,8H), 6.89-7.09 (br, s, 4H, NH); ¹³C NMR (50 MHz, CDCl₃): 137.26, 103.75,39.18, 33.21, 26.04, 8.65; HR-MS (EI) for C₃₂H₄₄N₄: calcd: 484.3565,found: 484.3561.

[0077] 2b: ¹HNMR (200 MHz, CDCl₃): δ=0.72-0.85 (t, J=8.37, 3H. —CH₂ CH₃), 1.53 (s, 3H, -CH₃), 1.92-2.06 (q, J=4.65, 6.97 Hz, 2H, —CH ₂CH₃),6.0-6.10 (m, 4H, pyrrole-βH), 6.50-6.58 (m, 2H,pyrrole-αH), 7.6 (BR, S,2H, pyrrole-NH). ¹³C NMR: 138.04, 116.29, 107.61, 104.66, 39.35, 33.63,25.57, 8.91; HR-MS (EI) for C₁₂H₁₆N₂: calcd: 188.1313, found: 188.1317.

Example 5

[0078] Synthesis of Octaethyl Calix (4) Pyrrole

[0079] In a 50 ml round bottom flask 20 ml of dichloromethane (DCM) wasintroduced and 0.5 ml of pyrrole, 0.73 ml of 3-Pentanone, and 0.5 g ofAl-MCM-41 catalyst was added to it. Then the mixture was refluxed for 5days. The cooled reaction mixture filtered, washed with DCM (5×10 ml).Then the solvent DCM was removed under reduced pressure and product waspurified by column chromatography on silicagel (hexane eluent) theproducts were confirmed by NMR and estimation was done by high pressurethin layer chromatography (HPTLC). The results as follows: conversion ofpyrrole is 77.0%. Product Yield (wt %) Selectivity (%) Octaethylcalix(4)pyrrole (3a) 10.1 13.1 Trimer + tetramer 4.8 6.2 Dimer (3b) 62.180.7

[0080] 3a: ¹HNMR (200 MHz, CDCl₃): δ=5.85-5.93 (br, d, J (H,H)=2.27 Hz,8H, pyrrole-βH), 6.96-7.05 (br, s, 4H, pyrrole-NH); HR-MS (EI) forC₃₆H₅₂N₄: calcd: 540.4191, found: 540.4194.

[0081] 3b: ¹HNMR (200 MHz, CDCl₃): δ=0.68-0.76 (t, J=7.17, 6H, CH₂ CH₃), 1.88-2.01 (q, J=5.12, 7.69 Hz, 4H, CH ₂CH₃), 6.01-6.12 (br, s, 4H,pyrrole-βH), 6.5-6.59 (br, s, 2H), 7.45-7.65 (br, s, 2H, pyrrole-NH);HR-MS (EI) for C₁₃H₁₉N₂: calcd: 202.1469, found: 202.1475.

Example 6

[0082] Synthesis of Tetraspiro Cyclohexyl Calix (4) Pyrrole

[0083] In a 50 ml round bottom flask 20 ml of dichloromethane (DCM) wasintroduced and 0.5 ml of pyrrole, 0.75 ml of Cyclohexanone, and 0.5 g ofcalcined and dried Al-MCM-41 catalyst was added to it. Then the mixturewas refluxed for 10 h The cooled reaction mixture filtered, washed withDCM (5×10 ml). Then the solvent DCM was removed under reduced pressureand product was purified by column chromatography on silicagel (hexaneeluent) the products were confirmed by NMR and estimation was done byhigh pressure thin layer chromatography (HPTLC). The results as follows:conversion of pyrrole is 95.0%. Product Yield (wt %) Selectivity (%)Tetraspirocyclohexyl 70.3 74.0 calix(4)pyrrole (4a) Trimer + tetramer12.4 13.0 Dimer (4b) 12.3 13.0

[0084] 4a: ¹H NMR (200 MHz, CDCl₃): δ=1.38-1.68(m,24H, cyclohexyl),1.88-2.12(m,16H, cyclohexyl), 5.86 (br.d, 8H; pyrrole-βH), 6.95 (br.s,4H, pyrrole NH), ¹³C NMR (50 MHz,CDCl₃): δ=22.75, 26.04, 37.17, 39.63,103.44 (pyrrole-βH), 136.50(pyrrole-αH); HR-MS(EI) for C₄₀H₅₂N₄ (H⁺):calcd: 588.4191; found: 588.4169.

Example 7

[0085] In a 50 ml round bottom flask 20 ml of dichloromethane (DCM) wasintroduced and 0.5 ml of pyrrole, 0.75 ml of Cyclohexanone, and 0.5 g ofHZSM-5 (30) catalyst was added to it. Then the mixture was refluxed for10 h. The cooled reaction mixture filtered, washed with DCM (5×10 ml).Then the solvent DCM was removed under reduced pressure and product waspurified by column chromatography on silicagel (hexane eluent) theproducts were confirmed by NMR and estimation was done by high pressurethin layer chromatography (HPTLC). The results as follows: Conversion ofpyrrole is 69.6%. Product Yield (wt %) Selectivity (%)Tetraspirocyclohexyl 10.7 15.4 Calix(4)pyrrole Trimer + tetramer 5.9 8.5Dimer 53.0 76.1

Example 8

[0086] In a 50 ml round bottom flask 20 ml of dichloromethane (DCM) wasintroduced and 0.5 ml of pyrrole, 0.75 ml of Cyclohexanone, and 0.5 g ofHY catalyst was added to it. Then the mixture was refluxed for 10 h. Thecooled reaction mixture filtered, washed with DCM (5×10 ml). Then thesolvent DCM was removed under reduced pressure and product was purifiedby column chromatography on silicagel (hexane eluent) the products wereconfirmed by NMR and estimation was done by high pressure thin layerchromatography (HPTLC). The results as follows: conversion of pyrrole is78.9%. Product Yield (wt %) Selectivity (%) Tetraspirocyclohexylcalix(4) pyrrole Trimer + tetramer 16.2 20.5 Dimer 62.7 79.5

[0087] 4b: ¹H NMR (200 MHz, CDCl₃): δ=1.36-1.65(m,6H,cyclohexyl),95-2.12(m,4H,cyclohexyl),6.01-6.12(m,4H,pyrrole-βH),6.45(br.d, 2H; pyrrole-αH), 7.32-7.68 (br.s, 2H, pyrrole NH); ¹³C NMR(50MHz,CDCl₃):δ=22.17,26.32,37.65, 41.21, 104.64, 108.27,116.99,139.21;HR-MS(EI) for C₁₄H₁₈N₂ (H⁺): calcd: 214.1469; found: 214.1460.M+:214(100%), 171,148

[0088] 4d: HR-MS (EI) for C H N: calcd: 508.3546; found=508.3565

Example 9

[0089] Synthesis of Tetraspiro Cyclopentyl Calix (4) Pyrrole

[0090] In a 50 ml round bottom flask 20 ml of dichloromethane (DCM) wasintroduced and 0.5 ml of pyrrole, 0.64 ml of Cyclopentanone, and 0.5 gof Al-MCM-41 catalyst was added to it. Then the mixture was refluxed for20 h. The cooled reaction mixture filtered, washed with DCM (5×10 ml).Then the solvent DCM was removed under reduced pressure and product waspurified by column chromatography on silicagel (hexane eluent) theproducts were confirmed by NMR and estimation was done by high pressurethin layer chromatography (HPTLC). The results as follows: conversion ofpyrrole is 74.3%. Product Yield (wt %) Selectivity (%) Tetraspirocyclopentyl 62.7 84.4 calix(4)pyrrole (5a) Trimer + tetramer 7.3 9.8Dimer 4.3 5.8

[0091] 5a: ¹HNMR (200 MHz, CDCl₃): δ=1.55-1.8 (m, 16H, cyclopentyl),1.85-2.01 (m, 16H, cyclopentyl), 5.8 (br, d, J=0.38 Hz, 8H,pyrrole-βH),7.0 (br, s, 4H, pyrrole-NH); ¹³C NMR: (50 MHz, CDCl₃):137.20 (pyrrole-αH), 103.04 (pyrrole-βH), 46.93, 39.02, 23.91; HR-MS(EI) for C₃₆H₄₄N₄: calcd: 532.3565, found: 532.6575.

Example 10

[0092] Synthesis of Tetraspiro Cycloheptyl Calix (4) Pyrrole

[0093] In a 50 ml round bottom flask 20 ml of dichloromethane (DCM) wasintroduced and 0.5 ml of pyrrole, 0.85 ml of Cycloheptanone, and 0.5 gof Al-MCM-41 catalyst was added to it. Then the mixture was refluxed for3 days. The cooled reaction mixture filtered, washed with DCM (5×10 ml).Then the solvent DCM was removed under reduced pressure and product waspurified by column chromatography on silicagel (hexane eluent) theproducts were confirmed by NMR and estimation was done by high pressurethin layer chromatography (HPTLC). The results as follows: conversion ofpyrrole is 69.8%. Product Yield (wt %) Selectivity (%) Tetraspirocycloheptyl 26.7 38.3 calix(4)pyrrole (6a) Trimer + tetramer 15.7 22.5Dimer (6b) 27.4 39.2

[0094] 6a: ¹HNMR (200 MHz, CDCl₃): δ=1.45-1.72 (m, 32H, cycloheptyl),1.94-2.12 (m,16H, Cycloheptyl), 5.83 (br, d,8H, pyrrole-βH), 6.78-6.88(br,s,4H,NH),; HR-MS (EI) for C44H₆₀N₄: calcd: 644.4817, found:644.4752.

[0095] 6b: ¹HNMR (200 MHz, CDCl₃): δ=2.12-2.26(m,8H,cycloheptyl),2.42-2.58 (m,4H, cycloheptyl), 6.01-6.13 (m, 4H,pyrrole-βH), 6.52-6.61(m,2H, pyrrole-αH),7.51-7.71 (br,s,2H, pyrrole-NH); HR-MS (EI) forC₁₅H₂₀N₂: calcd: 228.1626, found 228.1616.

Example 11

[0096] Synthesis of Tetraspiro Cyclo Octyl Calix (4) Pyrrole

[0097] In a 50 ml round bottom flask 20 ml of dichloromethane (DCM) wasintroduced and 0.5 ml of pyrrole, 0.9 ml of Cyclooctanone, and 0.5 g ofAl-MCM-41 catalyst was added to it. Then the mixture was refluxed for5days. The cooled reaction mixture filtered, washed with DCM (5×10 ml).Then the solvent DCM was removed under reduced pressure and product waspurified by column chromatography on silicagel (hexane eluent) theproducts were confirmed by NMR and estimation was done by high pressurethin layer chromatography (HPTLC). The results as follows: conversion ofpyrrole is 78.0%. Product Yield (wt %) Selectivity (%) Tetraspirocyclooctyl  8.3 10.6 calix(4)pyrrole (7a) Trimer + tetramer 23.7 30.4Dimer (7b) 46.0 59.0

[0098] 7a: ¹HNMR (200 MHz, CDCl₃): δ=1.18-1.82 (m, 56H, cyclooctyl),5.93 (br,d,8H, pyrrole-βH), 6.91-6.99 (br,s,4H, pyrrole-NH); HR-MS (EI)for C₄₈N₆₈N₄: calcd; 700.5443, found: 700.5456.

[0099] 7b: ¹HNMR (200 MHz, CDCl₃): δ=1.42-1.80(m,10H, cyclooctyl),2.09-2.21(m,4H, cyclooctyl), 5.99-6.16 (m,4H,pyrrole-βH), 6.48-6.57(m,2H,pyrrole-αH),7.42-7.69(br,s,2H,pyrrole-NH),; HR-MS(EI) forC₁₆N₂₂N₂: calcd: 242.1782, found: 242.1777.

Example 12

[0100] Synthesis of Tetraspiro (2-Methylcyclohexyl) Calix (4) Pyrrole

[0101] In a 50 ml round bottom flask 20 ml of dichloromethane (DCM) wasintroduced and 0.5 ml of pyrrole, 0.875 ml of 2-Methyl cyclohexanone,and 0.5 g of Al -MCM-41 catalyst was added to it. Then the mixture wasrefluxed for 10 h. The cooled reaction mixture filtered, washed with DCM(5×10 ml). Then the solvent DCM was removed under reduced pressure andproduct was purified by column chromatography on silicagel (hexaneeluent) the products were confirmed by NMR and estimation was done byhigh pressure thin layer chromatography (HPTLC). The results as follows:conversion of pyrrole is 60.2%. Product Yield (wt %) Selectivity (%)Tetraspiro  5.1  8.5 (2-methylcyclohexyl) calix(4)pyrrole (8a) Trimer +tetramer 21.3 35.4 Dimer (8b) 33.8 56.1

[0102] 8a: HR-MS (EI) for C₄₄H₆₀N₄: calcd: 644.4817, found 644.4847.

[0103] 8b: ¹HNMR (200 MHz, CDCl₃): δ=0.8(d,3H,J(H,H)=7.2 Hz,CH₃),1.24-2.34(m,9H,cyclohexyl), 6.01-6.14 (m,4H,pyrrole-βH), 6.42-6.54(m,2H,pyrrole-αH),7.48(br,s,2H,pyrrole-NH); HR-MS (EI) for C₁₅H₂₀N₂:calcd: 228.1626, found: 228.1634.

[0104] The Main Advantages of the Present Invention Are:

[0105] 1. The present invention is an improved process that comprisesenvironmentally clean technology with low wastage, easy separable andreusability of the catalyst.

[0106] 2. This method provides a selective heterogeneous catalyst withlonger life.

[0107] 3. The catalysts used in this process are easily separable by thesimple filtration

[0108] 4. It also provides a method wherein the kind and composition ofcalix (4) pyrrole can be varied within limits by a proper selection ofcatalyst.

[0109] 5. Tetraspirocyclopentyl calix (4) pyrrole has been synthesizedfor the first time over the heterogeneous method as well as homogeneousmethod.

[0110] 6. Tetraspirocycloheptyl calix (4) pyrrole has been synthesizedfor the first time over the heterogeneous method as well as homogeneousmethod.

[0111] 7. Tetraspirocyclooctyl calix (4) pyrrole has been synthesizedfor the first time over the heterogeneous method as well as homogeneousmethod.

[0112] 8. Tetraspiro (2-Methylcyclohexyl) calix (4) pyrrole has beensynthesized for the first time over the heterogeneous method as well ashomogeneous method.

[0113] The Salient Futures of the Process are

[0114] i) the present invention provides an improved process thatcomprises environmentally clean technology with low wastage, easyseparable and reusability of the catalyst,

[0115] ii) the catalysts used in this process are easily separable bythe simple filtration,

[0116] iii) this process provides an eco-friendly method with higherselectivity,

[0117] iv) a method provides a selective heterogeneous catalyst withlonger life, and

[0118] v) a method wherein the kind and composition of calix(4)pyrrolecan be varied within limits by a proper selection of catalyst and thisinvention provides an efficient and economical method for synthesizingcalix(4)pyrroles from pyrrole and ketones over solid acid catalysts.

1. Novel compounds of substituted calix(4) pyrroles namely tetraspiro cycloheptyl calix (4) pyrrole , tetraspiro cyclooctyl calix (4) pyrrole and tetraspiro (2-methyl cyclohexyl) calix(4) pyrrole as shown in structural formulae 6a, 7a and 8a of the accompanying drawings, for use in many industrial applications particularly in biological applications.
 2. Novel compounds as claimed in claim 1, wherein the compounds having following properties. i) tetraspiro cycloheptyl calix (4) pyrrole (6a): ¹HNMR (200 MHz, CDCl₃): δ=1.45-1.72 (m, 32H, cycloheptyl), 1.94-2.12 (m,16H, Cycloheptyl), 5.83 (br, d,8H, pyrrole-βH), 6.78-6.88 (br,s,4H,NH),; HR-MS (EI) for C₄₄H₆₀N₄: calcd: 644.4817, found: 644.4752; ii) tetraspiro cyclooctyl calix (4) pyrrole (7a), ¹HNMR (200 MHz, CDCl₃): δ=1.18-1.82 (m, 56H, cyclooctyl), 5.93 (br,d,8H, pyrrole-βH), 6.91-6.99 (br,s,4H, pyrrole-NH); HR-MS (EI) for C₄₈N₆₈N₄: calcd; 700.5443, found: 700.5456; and iii) tetraspiro (2-methyl cyclohexyl) calix(4)pyrrole (8a): HR-MS (EI) for C44H60N₄: calcd: 644.4817, found 644.4847.
 3. A method for preparing substituted calix (4) pyrroles, said method comprising reacting a pyrrole with a acyclic and cyclic ketones over a mesoporus molecular sieve solid acid catalyst in presence of a solvent, at reflux temperature of about 100° C. for period ranging from 10 to 72 hours, recovering the solid products by filtration, washing with deionized water and drying in air and calcined at 773K in air.
 4. A method as claimed in claim 3 wherein, the catalyst is selected from MCM-41, HZSM-5 (30), Hβ, HY and SAPO-5.
 5. A method as claimed in claim 3 wherein, the amount of catalyst used is ranging from 0.1 g to 1.0 g.
 6. A method as claimed in claim 3 wherein, the catalysts used are having the following surface area and pore size as given below. Surface area Catalyst (m²/g) Pore size (° A) MCM-41  980-1200  30-100 HY 525-625 6-8 HZSM-5 (30) 275-340   5-7.5 SAPO-5 175-240 6.5-8.4 Hβ 600-680 5.5 × 6.6 to 7.5 × 8.5


7. A method as claimed in claim 3 wherein, the pore size and surface area of the catalysts used in the reaction are given in the following table. Catalyst Surface area (m²/g) Pore size (° A) HY 593 7.3 HZSM-5 (30) 310 5.6 SAPO-5 207 7.4 Hβ 640 6.5 × 7.6


8. A method as claimed in claim 3 wherein, the solvent used for refluxing is selected from dichloromethane, methanol, and acetonitrile.
 9. A method as claimed in claim 3 wherein, the molar ratio of pyrrole to ketone is selected in between 1:1 to 1:4.
 10. A method as claimed in claim 3 wherein, the cycloketone is selected from the group comprising cyclohexanone, cycloheptanone, cyclopentanone and cyclooctanone.
 11. A method as claimed in claim 3 wherein acyclic ketone is selected from the group comprising methyl ethyl ketone and 3-pentanone.
 12. A method as claimed in claim 3 wherein, acyclic products are obtained using the catalyst HY.
 13. A method as claimed in claim 3 wherein, major amounts of liner products are obtained using catalyst HZSM-5 (30).
 14. A method as claimed in claim 3 wherein, the yield of the calix (4) pyrrole is up to 70%.
 15. A method as claimed in claim 3 wherein, the selectivity of the calix (4) pyrrole is up to 90%.
 16. A method as claimed in claim 3 wherein, the calix (4) pyrrole obtained are: i) octamethyl calix (4) pyrrole (1a); ii) Tetraethyl Tetra methyl calix (4) pyrrole (2a); iii) octaethyl calix (4) pyrrole (3a); iv) tetraspiro cyclohexyl calix (4) pyrrole (4a); v) tetraspiro cyclopentyl calix (4) pyrrole (5a); vi) tetraspiro cycloheptyl calix (4) pyrrole (6a), vii) tetraspiro cyclooctyl calix (4) pyrrole (7a); viii) (2-methyl cyclohexyl) calix (4) pyrrole (8a) and ix) dimer, trimer and tetramers of pyrroles
 17. A method for preparing calix (4) pyrroles or tetraspiro calix (4) pyrroles, said method comprising mixing a pyrrole with a acyclic or cyclic ketones over a molecular sieve solid acid catalyst and subjecting the mixture to microwave radiation for 3 to 10 minutes and optionally, refluxing using a solvent for extracting the compounds.
 18. A method as claimed in claim 17 wherein, the solvent used for refluxing is selected from dichloromethane, methanol, and acetonitrile.
 19. A method as claimed in claim 17 wherein, the molar ratio of pyrrole to ketone is 1:1.
 20. A method as claimed in claim 17 wherein, in the reaction of equimolar ratio of pyrrole and cyclohexanone, dichloromethane is used as a solvent for refluxing to obtain cyclic products.
 21. A method as claimed in claim 17 wherein, the catalyst used is mesoporus molecular sieve catalyst (MCM-41).
 22. A method as claimed in claim 17 wherein, the mesoporus catalyst used in the reaction is having surface area ranging between 980-1200 m²/g.
 23. A method as claimed in claim 17 wherein, the mesoporus catalyst used in the reaction is having pore size ranging between 30-100° A.
 24. A method as claimed in claim 17 wherein, the microwave heating is carried out for a period ranging from 2 minutes to 15 minutes, more preferably 3 to 10 minutes.
 25. A method as claimed in claim 17 wherein, the microwave radiation level is at about 2450 MHz.
 26. A method as claimed in claim 17 wherein, the acyclic ketone used is acetone.
 27. A method as claimed in claim 17 wherein, the cyclic ketone used is cyclohexanone.
 28. A method as claimed in claim 17 wherein, the preparation of calix (4) pyrroles or tetraspiro calix (4) pyrroles is a solvent free process.
 29. A method as claimed in claim 17 wherein, the calix (4) pyrrole obtained are: i) octamethyl calix (4) pyrrole (1a); ii) Tetraethyl Tetra methyl calix (4) pyrrole (2a); iii) octaethyl calix (4) pyrrole (3a); iv) tetraspiro cyclohexyl calix (4) pyrrole (4a); v) tetraspiro cyclopentyl calix (4) pyrrole (5a); vi) tetraspiro cycloheptyl calix (4) pyrrole (6a), vii) tetraspiro cyclooctyl calix (4) pyrrole (7a); viii) (2-methyl cyclohexyl) calix (4) pyrrole (8a); and ix) dimer, trimer and tetramers of pyrroles 